Gloomy outlook aside, European analyzer introductions continue - immunoassay analyzers

More than 50 countries were represented at the 9th International Colloquium held at Pont-a-Mousson, France. This is an unusual meeting which provides a discussion platform for future ideas and developments in clinical biology. For more than 2,000 biologists, mostly from European clinical laboratories, this was an opportunity to compare notes on the growing economic difficulties facing laboratories in Europe.

Continuing and growing public health deficits in most West European countries (see story, page 233) are ensuring that existing pressures for cost containment will continue and probably will intensify. The result in clinical diagnostics is to force the pace toward further consolidations of laboratory test sites and more moves toward automation of sample handling and diagnostic procedures. Numbers of diagnostic procedures continue to grow, but European sales revenues for 1996 are projected to fall by 1.5% to 2.5% compared to 1995 levels. Immunoassay sales, which grew in 1994 and 1995 by about 3% each year, are expected to drop by close to 2% in 1996 (see Table 4).

In spite of uncertain market prospects, however, new instrumentation systems continue to arrive on the market. It is noteworthy that those being introduced today tend to be labor-saving systems that can pay for themselves.

Immunoassay analyzer developments

With at least 15 systems launched in Europe since 1993, immunoassay suppliers are continuing to press forward with new models and, more strikingly, with the development of wider ranges of analytes. For these 15 systems alone, immunoassay suppliers are projecting to launch 233 new analytes in 1997, an increase of just under 65% over 1996 levels (Table 5 on page 231). Chiron Diagnostics (Emeryville, California), Ortho Diagnostic Systems (Raritan, New Jersey) and Sanofi Diagnostics Pasteur (Marnes-la-Coquette, France) each plan to bring more than 30 new tests to the European market next year.

Table 4

European Immunoassay Markets

Country         1995 Revs.       Actual Change,         Projected
               ($ million)          1993-95          Change,
1995-96

France             415               +11.0%                -1%
Germany            575               +12.0%                -2%
Italy              365                -7.5%                -3%
Spain              165                +5.5%                -1%

Source: The BBI Newsletter

With the exception of the Unicap 100 allergy test analyzer priced at $29,000 from Pharmacia & Upjohn (Uppsala, Sweden), all of the other new immunoanalyzers launched this year have been priced in excess of $100,000. All can handle at least 15 parameters simultaneously; the ACS Centaur from Chiron Diagnostics and the Magia 120 from Merck Diagnostic (Darmstadt, Germany) accommodates up to 30 tests at once.

Differences in marketing priorities

Wide differences can be seen in the analyte priorities that have been given by competing suppliers in developing their lines of tests (Table 6 on page 232). That table, which includes both the present lines and new assays announced for launch in 1997, shows that almost all suppliers offer good coverage of thyroid assays and tumor marker tests, while a majority also have developed comprehensive lines of fertility and anemia tests.

Abbott Diagnostics (Abbott Park, Illinois), Bayer Diagnostics (Munich, Germany), Chiron Diagnostics and Dade International (Dudingen, Switzerland) have included TDM (therapeutic drug monitoring) capabilities, with Abbott also offering 11 drugs of abuse (DOA) parameters. Most European-developed analyzers have tended to exclude TDM/DOA capabilities, which often have been included on their clinical chemistry analyzers, using sublicensed Syva (San Jose, California) homogenous assay technology.

Another specialized area is that of infectious disease testing, with Abbott Diagnostics, Ortho Diagnostic, Roche Diagnostic Systems (Montclair, New Jersey) and Sanofi Diagnostics Pasteur all offering a wide choice of analytes. The Access analyzer from Sanofi includes assays for a wide range of immunoproteins, as well as rheuma screening tests for CRP, ASO and RF. BioMerieux (Marcy l'Etoile, France) has included three coagulation assays in its line. CIS Bio International (Gif-sur-Yvette, France) plans to launch three osteoporosis tests in 1997 for its new Kryptor analyzer, while Bio-Rad (Hercules, California) will add two new autoimmune assays for ENA and DsNA to its existing ANA test next year.

With more than 10,000 automated immunoassay analyzers installed in France alone, each manufacturer is seeking to maximize system advantages by differentiating its test palette to target specific laboratory sectors, with the potential client presented with an increasingly wide range of options and choices.

Origins of homogenous immunoassay system

CIS Bio International is the in vivo and in vitro diagnostics arm of Group Oris (Gif-sur-Yvette, France), which in turn embodies the commercial activities of the giant French nuclear agency, Commissariat a l'Engergie Atomique. Groupe Oris owns 30% of Canberra Industries (Meriden, Connecticut), which has as a subsidiary Packard Instrument (Downers Grove, Illinois). All three companies have been involved in a 10-year development program which has resulted in the novel Trace (time resolved amplified cryptate emission) methodology and the Kryptor analyzer.

The Trace research program was based on fundamental research on rare earth ion cryptates by Professor Jean-Marie Lehn of the University Louis Pasteur (Strasbourg, France), for which he received the Nobel Prize in chemistry in 1987. The chemistry of cryptates makes possible direct assays in a single liquid solution without any separation steps being necessary. Just as importantly, with the Trace method a wide spectrum of molecular sizes can be detected. Europium cryptate is the energy donor in the Trace system, with the accepting fluorophore being a phycobilisome XL 665 which is extracted from red algae. Conjugation can be to an antibody, antigen or a hapten, without loss of immunoreactivity.

In an immunometric assay, for instance, a europium derivative is conjugated to a highly specific antibody, with a second highly specific antibody linked to the fluorophore. The immunocomplex is excited at 337nm, using a laser, the amplified energy transfers from the donor cryptate to the acceptor fluophore, and is detected as a long-lived signal at 665nm.

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Future application to trace methodology

Because Trace methodology uses direct assay techniques which are not limited in application by analyte molecule size, they can be integrated into multi-parametric instruments. Such systems could perform on a single sample almost all assays possible in clinical chemistry, immunology, serology of infectious diseases, or hemostasis.

Some of these potential applications still have not been indentified, but there already is a recognition among pharmaceutical research groups that the simplicity of Trace technology can significantly reduce research costs. CIS Bio International already has set up several special application contracts with leading pharmaceutical companies in this area. In some cases, the reagents will need to be developed specifically for a particular assay requirement, with varying needs for labeling and combining. This is an area where Packard Instrument, a well-known supplier to the medical research sector, will be a natural partner for CIS Bio.

Automated blood culture systems

The rapid isolation and identification of organisms responsible for bacteremia and septicemia is a major and important activity in microbiology laboratories. Since the prognosis for such infections is generally not good, with a high mortality rate, it is important that diagnosis be made as soon as possible so that the appropriate antibiotic treatment can be started.

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Automated blood culture systems that have been developed all have the aim of improving the sensitivity and speed of detection, as compared to traditional blood culture flask systems. Of the four systems listed in Table 7, only the BioArgos Elite from Sanofi Diagnostics Pasteur is fully automated, with the other three instruments being semi-automated. With the BioArgos system, a sterile, single-use sampling device consisting of needle, tubing and bell takes samples from Vacutainer tubes and inoculates the blood bottles automatically. Subsequent stages of incubator loading, preheating, reading and measurement all are [TABULAR DATA FOR TABLE 7 OMITTED] automated. Controlled by preset programming, positive flasks are retained at 37 [degrees] C, while negative flasks are automatically ejected into a disposal container. The other three systems require manual loading and discharge from the incubator unit.

Traditionally, bacteriology has been a very important sector in clinical laboratories, but a sector in which instrumentation and automation have had limited impact. Techniques have shown few changes from established methodologies, and Louis Pasteur himself would find little difficulty in recognizing many of the tests still used today. Although these methods often are labor-intensive, expensive and not very fast, the impact of sophisticated automated systems has been limited. In France, for example, which has the highest acceptance level for commercial pre-pour, ready-to-use bacteriology plates, tubes and flasks, there are only 80 automated blood culture systems installed. The price level for complete systems, including incubators and control software, is $90,000 to $100,000 in Europe, and microbiology laboratories, which in the past have demanded only limited capital investment, may have problems justifying that level of expenditure.

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